Fig 5. Oligomycin-containing nanoparticles targeted to monocytes induce metabolomic changes in MDSCs.
C57BL/6NCrl mice received a single intra-articular injection of Cy5/Tuftsin (CT) or Cy5/Tuftsin/Oligomycin (CTO) nanoparticles (10 μg) at day 7 post-infection (n = 5 mice/treatment group). Mice were sacrificed 3 days following nanoparticle injection and MDSCs (CD11bhighLy6G+Ly6C+F4/80-) were recovered from each individual animal by FACS, whereupon intracellular metabolites were isolated for analysis by HPLC-MS/MS. (A) A principle component analysis (PCA) plot was generated using an algorithm in MetaboAnalyst with mean intensities and pareto scaling distribution. Ellipses represent a 95% confidence interval of the normal distribution for each cluster. (B) The heat map depicts the top 25 metabolite differences in MDSCs recovered from CTO and CT treated mice. The color key indicates log2-fold changes of normalized mean peak intensities for metabolites in MDSCs from CTO vs. CT nanoparticle treated animals. (C) Identification of the most significantly altered pathways in MDSCs isolated from CTO treated mice as determined by pathway impact analysis.